reduced pressure and the residue was treated with 2% HCl in
DME, giving rise to the adduct 7. The crude product 7 was
subsequently treated with ClCH2OMe and Pri2NEt in CH2Cl2 to
afford the protected bromoquinone 8 as light yellow crystals
(mp 169–172 °C) in 85% overall yield. Subsequent conversion
of 8 to the aminonaphthoquinone 10 was accomplished by the
reaction of 8 with NaN3 and PPh3 in DMSO followed by
treatment of the resulting iminophosphorane 9 with aqueous
formaldehyde in THF. Thus the desired aminonaphthoquinone
10 was obtained as red crystals (mp 177–179 °C) in 68% yield.
Although compound 10 is itself the naphthoquinone core of
streptovaricin U 1, it is necessary to further transform it into the
naphthalene derivative 13 for the coupling reaction with the
ansa chain segment, since the amino group on a naphthoquinone
ring such as 10 is not sufficiently basic for further transforma-
tion. The conversion of 10 into the target molecule 13 was,
however, unexpectedly troublesome and required ingenuity.
Eventually the desired transformation was overcome by the
following reaction sequence. Hydrogenation of 10 over Adams’
catalyst in EtOH in the presence of di-tert-butyl dicarbonate
(Boc2O) followed by treatment with oxygen gave rise to the
N-Boc-aminonaphthoquinone 11 as light yellow crystals (mp
141–143 °C) in 85% yield. The product 11 was subsequently
converted to the naphthalene dimethyl ether 12 (mp
104–106 °C) by hydrogenation over Adams’ catalyst in EtOH
followed by treatment of the resulting dihydroquinone with
dimethyl sulfate and 1 m NaOH in 83% yield. The synthesis of
the fully functionalized aromatic core 13 of streptovaricin U 1
was accomplished by removal of the Boc group in 12 by
thermolysis in Ph2O at 185 °C (sealed tube), resulting in
formation of 13 in 87% yield.
This work was also supported by a Grant-in-Aid for
Scientific Research on Priority Areas (No. 08245101) and a
Grant-in-Aid for Scientific Research (No. 09874149) from the
Ministry of Education, Science, Sports, and Culture of Japan.
Footnotes and References
* E-mail: miyasita@schem.ec.hokudai.ac.jp
† All new compounds exhibited satisfactory spectra (1H and 13C NMR, IR)
and elemental analyses.
1 K. L. Reinhart, Jr. and L. S. Shield, Fortschr. Chem. Org. Naturst., 1976,
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Thus an efficient and regioselective synthesis of the naph-
thoquinone core of streptovaricin U 1 has been established. The
overall yield of 13 from the dibromoquinone 6 was 35%. The
manipulations employed in the conversion of 10 into 13 may be
widely applicable to the synthesis of various aminonaphthoqui-
nones. The coupling reaction of the aromatic core 13 with the
ansa chain segment toward the total synthesis of 1 is now in
progress.
8 B. M. Trost and W. H. Pearson, Tetrahedron Lett., 1983, 24, 269.
Received in Cambridge, UK, 1st July 1997; 7/04596D
1788
Chem. Commun., 1997